Journal Article

New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies


GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotype–phenotype correlation of these structural variants remains to be established. Our data expand the spectrum of GJA8 variants and associated phenotypes, confirming the importance of this gene in early eye development.

Attached files


Ceroni, Fabiola
Aguilera-Garcia, Domingo
Chassaing, Nicolas
Bax, Dorine Arjanne
Blanco-Kelly, Fiona
Ramos, Patricia
Tarilonte, Maria
Villaverde, Cristina
Rodrigues Jacy da Silva, Luciana
Ballesta-Martinez, Maria Juliana
Sanchez-Soler, Maria Jose
Holt, Richard James
Cooper-Charles, Lisa
Bruty, Jonathan
Wallis, Yvonne
McMullan, Dominic
Hoffman, Jonathan
Bunyan, David
Stewart, Alison
Stewart, Helen
Lachlan, Katherine
Fryer, Alan
McKay, Victoria
Roume, Joëlle
Dureau, Pascal
Saggar, Anand
Griffiths, Michael
Calvas, Patrick
Ayuso, Carmen
Corton, Marta
Ragge, Nicola K.

Oxford Brookes departments

Faculty of Health and Life Sciences\Department of Biological and Medical Sciences


Year of publication: 2018
Date of RADAR deposit: 2018-03-12

Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License

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